Is gender identity – the sense of being a man or a woman – a perception identical with the nonconscious physical brain or the conscious non-physical soul? Since people who identify as transsexual verbally self-report strong feelings of being the opposite sex and a feeling that their sexual characteristics are not constitutive of their actual gender, they are a powerful case in explaining the nature of gender identity and phenomenal consciousness.

It is possible that a person’s sense of gender identity may be subserved by an
nonconscious physical base with a specific neurophysiological or neural ‘signature’. Explaining gender identity in this direct way aims first to describe the base as a correlate of gender identity, then ultimately to achieve a reductive neurophysiological explanation of gender identity.

Neurophysiological mechanism and transexual experiences can be correlated for a variety of reasons: the mechanism is part of the cause of transexualism; the mechanism is part of the effect of transsexualism; the mechanism indirectly parallels transsexualism; the mechanism is what transsexualism can be identified with. Discovering the neurophysiological signature of transsexualism requires the identification of some neurophysiological mechanism with transsexualism. The correlation of mechanism x with transsexualism is informative because x may be the one for identifying transsexualism. Correspondingly, mechanism y that does not correlate with transsexualism indicates that y may not be the one. If there is a mechanism of transsexualism with a neurophysiological signature identifiable with transsexual experiences, the scientific and clinical benefits could be huge. Thus, investigating transsexualism directly is worth a try.

There is support for theoretical identification of gender identity with neurophysiological mechanism. According to the most influential theory, during the intrauterine period, two mechanical operations may occur: (1) in the female ‘direction’, there is no surge of testosterone on nerve cells; (2) in the male ‘direction’, there is a surge of testosterone on nerve cells. Since sexual differentiation of the brain occurs in the second half of pregnancy, and sexual differentiation of the sexual organs occurs in months 1-2 of pregnancy, transsexuality may result. Thus, the relative masculinzation of the brain at birth may not reflect the relative masculinization of the genitals (e.g., Berenbaum & Beltz, 2011; Savic et al. 2011; Veale et al. 2010).

One line of neuroscientific support for a neuroanatomical signature of gender identity derives from studies on whether gray matter volumes in (heterosexual) male-to female (MTF) transexuals before cross-sex hormonal treatment are correlated with people who share their biological sex (i.e., men), or people who share their gender identity (i.e., women). Luders et al. (2009) analyzed MRI data of 24 male-to-female (MTF) transsexuals and found that regional gray matter variation in MTF transsexuals correlates with the pattern found in men than in women. Luders et al. (2012) found thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus) than age-matched control males.

In contrast, Rametti et al. (2011) found that the white matter microstructure pattern in MTF transsexuals is halfway between the pattern of examined male and female controls. These differences may indicate that some fasciculi do not complete the masculinization mechanical operation in MTF transsexuals during foetal brain development. This implies that the social environment is co-constitutive of gender identity. Clearly, more research is needed to answer this question.

Another line of neuroscientific research has focused on intrinsic brain activity (i.e., brain resting-state) to investigate correlations between the spontaneous brain connectivity of transexuals and control groups. Santarnecchi et al. (2012) used both seed-voxel and atlas-based region-of-interest (ROI) approaches and found that brain regions sensitive to gender dimorphism (e.g., left lingual gyrus, precuneus) revealed robust correlations between the female-to-male (FTM) subject and female control group with regard to control males, with comparable extension and location of functional connectivity maps. ROI analysis supported this result, demonstrating an increased pattern of differences between the FTM subject and males and the FTM subject and females. No statistically significant difference was found between seed-voxel results in the FTM subject and females. This study supports the hypothesis that untreated FTM transgender shows a functional connectivity profile comparable to female control subjects.

Taken together, these findings provide evidence that transsexualism is correlated with a specific physical signature, in terms of neuroanatomy and brain connectivity, which supports the claim of mind-brain identity theory that neurophysiological mechanism is constitutive of gender identity. Thus, the most reasonable explanation of transsexualism and gender identity is that it is entirely physical in nature.